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Immune Response to HPV Vaccine Lower in Girls With Than Without HIV
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4th International Workshop on HIV & Women, January 13-14, 2014, Washington DC
Mark Mascolini
HIV-positive girls 9 to 13 years old had lower peak geometric mean titer (GMT) responses to the quadrivalent human papillomavirus (HPV) than HIV-negative girls in a published comparison group [1]. But GMTs against the four HPV types targeted by the vaccine in the girls with HIV were comparable to those of HIV-negative 18- to 26-year-old women in whom quadrivalent vaccine efficacy has been demonstrated.
US authorities recommend the quadrivalent HPV vaccine for all girls and boys starting as early as age 9 and for young women and men with a weakened immune system, including those with HIV infection [2]. But little is known about the safety and immunogenicity of the quadrivalent vaccine in girls or boys with HIV infection. The quadrivalent and bivalent vaccines are effective against diseases caused by the HPV types they cover. HPV 16 and 18 cause most cervical and anal cancers, as well as other cancers.
To learn more about HPV vaccine responses in HIV-positive girls, Canadian researchers conducted a subanalysis of a quadrivalent vaccine trial in HIV-positive girls and young women, including 32 girls 9 to 13 years old. All girls were assigned to receive three doses of the quadrivalent vaccine at 0, 2, and 6 months and to be evaluated for GMT at months 7, 12, 18, and 24. The investigators compared results in these 32 girls with responses in 252 HIV-negative Canadian girls who got the quadrivalent vaccine in another trial [3].
All but one of the HIV-positive girls was seronegative for the four HPV types covered by the HPV vaccine (6, 11, 16, and 18), and all completed the three-dose vaccine course. Age averaged 11 years in these girls. Among girls whose race was reported, most (70%) were black and 26% were Asian. The group had a median baseline CD4 count of 692 (interquartile range [IQR] 547 to 960) and a median nadir CD4 count of 442 (IQR 246 to 594). An average 9 years had passed since their HIV diagnosis. Most girls were taking antiretroviral therapy, and 19 (59%) had an undetectable viral load when they got their first vaccine dose.
No vaccine-related serious adverse events arose in any girl with HIV. All initially HPV-negative girls with HIV seroconverted for each of the four vaccine types. In an age-adjusted analysis comparing these HIV-positive girls with HIV-negative girls in the previous trial [3], peak GMTs against each vaccine type at month 7 were significantly lower in the girls with HIV:
GMTs in 9-to-13-year-old girls with vs without HIV:
HPV 16: 4382 vs 7650 mMu/mL, P < 0.01
HPV 18: 640 vs 1703 mMu/mL, P < 0.001
HPV 6: 830 vs 1856 mMu/mL, P < 0.001
HPV 11: 977 vs 2096 mMu/mL, P < 0.0001
The researchers noted that the GMTs in these HIV-positive girls are comparable to GMTs in 18- to 26-year-old HIV-negative women in whom the quadrivalent vaccine proved effective. But among 16 HIV-positive girls with follow-up through 24 months, GMTs against HPV 16, 18, 6, and 11 had dwindled to 628, 55, 101, and 105 mMu/mL. Respective GMTs in 186 HIV-negative girls at month 24 were 1739, 267, 359, and 422 mMu/mL, and all differences from the HIV-positive group were highly significant.
A recently published study of the quadrivalent vaccine in 99 HIV-positive US women 16 to 23 years old found GMTs equivalent to those of an HIV-negative comparison group in the 30 women taking antiretroviral therapy [4]. Among antiretroviral-treated women seronegative and HPV DNA negative for each type before vaccination, all seroconverted after vaccination. GMT and seroconversion rates were lower in the 69 untreated women with HIV than in the HIV-negative comparison group but still robust by historical standards. GMTs in the untreated young women were 2393 mMu/mL against HPV 16, 463 mMu/mL against HPV 18, 658 mMu/mL against HPV 6, and 727 mMu/mL against HPV 11.
In the Canadian study, month 7 GMTs against all four HPV types were significantly higher in girls with a viral load below 50 copies than in those with a detectable load, and these differences were statistically significant for HPV 11, 16, and 18.
The Canadian team cautioned that "until an immune correlate of protection is defined in HIV-negative and HIV-positive persons, understanding of the meaning of antibody levels remains limited." They suggested that booster dosing should be evaluated for girls and women with HIV.
References
1. Money D, Moses E, Dobson S, et al. Lower immune response in HIV positive girls to the qHPV vaccine. 4th International Workshop on HIV & Women, January 13-14, 2014, Washington DC. Abstract 15.
2. Centers for Disease Control and Prevention. Vaccines & immunizations. HPV vaccination. http://www.cdc.gov/vaccines/vpd-vac/hpv/default.htm
3. Dobson SR, McNeil S, Dionne M, et al. Immunogenicity of 2 doses of HPV vaccine in younger adolescents vs 3 doses in young women: a randomized clinical trial. JAMA. 2013;309:1793-1802.
4. Kahn JA, Xu J, Kapogiannis BG, et al. Immunogenicity and safety of the human papillomavirus 6, 11, 16, 18 vaccine in HIV-infected young women. Clin Infect Dis. 2013;57:735-744. http://www.ncbi.nlm.nih.gov/pubmed/23667266
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